BACKGROUND: Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART).
METHODS: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher\'s exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.
RESULTS: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039).
CONCLUSIONS: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.
BACKGROUND: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015).

Occupational exposure to diacetyl, a butter flavor chemical, can result in obliterative bronchiolitis. Obliterative bronchiolitis is characterized by exertional dyspnea, fixed airflow obstruction, and histopathologic constrictive bronchiolitis, with bronchiolar wall fibrosis leading to luminal narrowing and obliteration. We describe a case of advanced lung disease with histopathology distinct from obliterative bronchiolitis in a 37-year-old male coffee worker following prolonged exposure to high levels of diacetyl and the related compound 2,3-pentanedione, who had no other medical, avocational, or occupational history that could account for his illness. He began working at a coffee facility in the flavoring room and grinding area in 2009. Four years later he moved to the packaging area but continued to flavor and grind coffee at least 1 full day per week. He reported chest tightness and mucous membrane irritation when working in the flavoring room and grinding area in 2010. Beginning in 2014, he developed dyspnea, intermittent cough, and a reduced sense of smell without a work-related pattern. In 2016, spirometry revealed a moderate mixed pattern that did not improve with bronchodilator. Thoracoscopic lung biopsy results demonstrated focal mild cellular bronchiolitis and pleuritis, and focal peribronchiolar giant cells/granulomas, but no evidence of constrictive bronchiolitis. Full-shift personal air-samples collected in the flavoring and grinding areas during 2016 measured diacetyl concentrations up to 84-fold higher than the recommended exposure limit. Medical evaluations indicate this worker developed work-related, airway-centric lung disease, most likely attributable to inhalational exposure to flavorings, with biopsy findings not usual for obliterative bronchiolitis. Clinicians should be aware that lung pathology could vary considerably in workers with suspected flavoring-related lung disease.

Swyer-James-Macleod syndrome (SJMS) is a rare clinical entity acquired during childhood due to a respiratory infection leading to bronchiolitis obliterans. This inciting event is hypothesized to cause structural and functional changes of the developing alveoli, terminal bronchioles, and the corresponding pulmonary vasculature, resulting in emphysematous changes and a matched ventilation-perfusion defect. We present a 67-year-old male patient with hypercapnic respiratory failure requiring invasive mechanical ventilation, who had typical features of SJMS undiagnosed before this admission. He was extubated successfully, discharged home, and continues to be stable at a 90-day follow-up period. This marks one of the rare accounts where a patient with SJMS was given ventilatory support emergently, and one of the oldest patients reported. SJMS is under-reported due to its indolent clinical course and misdiagnosed as some other pulmonary abnormality. The clinical course progression and prognosis are unclear and variable in many affected patients due to this condition\'s rarity.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a pulmonary disease characterized by disruption of surfactant homeostasis resulting in its accumulation in the alveoli. PAP is classically classified into three categories (Table 1): 1/primary (or autoimmune) with antibodies targeting the GM-CSF pathway, 2/secondary to another disease, typically a hematologic malignancy, and 3/genetic.
METHODS: A 30 year-old woman received an allogenic hematopoietic stem cell transplantation (HSCT) after treatment for acute myeloid leukemia (AML). Within the first 6 months post HSCT, she developed an ocular, oral, digestive and hepatic graft-versus-host disease associated with a mixed ventilatory defect with a very severe obstructive syndrome and a severe CO diffusion impairment. High resolution computed tomography showed a classical \"crazy paving\" pattern. Aspect and differential cell count of BAL were normal. All microbiological samples remained culture negative. Histo-pathological analysis of transbronchial biopsies was unremarkable. Because of the severity of the respiratory insufficiency, open-lung biopsy (OBL) could not be performed. Despite multiple immunosuppressive therapies, lung function deteriorated rapidly; the patient also developed an excavated fungal lesion unresponsive to treatment. She underwent a bilateral lung transplant 48 months after HSCT. Histo-pathological analysis of explanted lungs showed obliterative bronchiolitis (OB), diffuse PAP and invasive cavitary pulmonary aspergillosis.
CONCLUSIONS: This case illustrates the simultaneous occurrence of OB, PAP and a fungal infection in a 30-year old female patient who underwent HSCT for acute myeloid leukemia (AML). To our knowledge this is the only documented case of PAP associated with OB treated by lung transplantation.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune condition characterized by erosive inflammation of the joints. One rare pulmonary manifestation is obliterative bronchiolitis (OB), a small airways disease characterized by the destruction of bronchiolar epithelium and airflow obstruction.
METHODS: We retrospectively reviewed the clinical data of patients with rheumatoid arthritis-associated obliterative bronchiolitis (RA-OB) from 01/01/2000 to 12/31/2015. Presenting clinical features, longitudinal pulmonary function testing, radiologic findings, and independent predictors of all-cause mortality were assessed.
RESULTS: Forty one patients fulfilled criteria for diagnosis of RA-OB. There was notable female predominance (92.7%) with a mean age of 57 ± 15 years. Dyspnea was the most common presenting clinical symptom. Median FEV1 was 40% (IQR 31-52.5) at presentation, with a mean decline of - 1.5% over a follow-up period of thirty-three months. Associated radiologic findings included mosaic attenuation and pulmonary nodules. A majority of patients (78%) received directed therapy including long-acting inhalers, systemic corticosteroids or other immunosuppressive agents, and macrolide antibiotics. All-cause mortality was 27% over a median follow-up of sixty-two months (IQR 32-113). No distinguishable predictors of survival at presentation were found.
CONCLUSIONS: RA-OB appears to have a stable clinical course in the majority of patients despite persistent symptoms and severe obstruction based on presenting FEV1.

BACKGROUND: Micronodular lesions are common findings in lung imaging. As an important differential diagnosis, we describe a case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia; it is notable that the diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is often delayed. This case provides supporting evidence to establish lung biopsy by cryotechnique as the option of first choice when considering a diagnostic strategy for micronodular lung lesions.
METHODS: We report a case of a 65-year-old white woman who presented with obstructive symptoms of chronic coughing and dyspnea confirmed by conventional lung function tests. A computed tomography scan presented disseminated micronodules in all the lobes of her lungs. With the help of bronchoscopic cryobiopsy it was possible to obtain a high yield sample of lung parenchyma. On histologic examination, the micronodules correlated with a diffuse neuroendocrine cell hyperplasia. In the context of clinical symptoms, radiological aspects, and histomorphological aspects we made the diagnosis of a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Obstructive symptoms were treated with inhaled steroids and beta-2-mimetics continuously. A comparison between current computed tomography scans of our patient and scans of 2014 revealed no significant changes. Last ambulatory checks occurred in January and May of 2016. The course of disease and the extent of limitation of lung function have remained stable.
CONCLUSIONS: The diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is best made in a multidisciplinary review including clinical presentation, lung imaging, and histomorphological aspects. This report and current literature indicate that transbronchial lung cryobiopsy can be used as a safe and practicable tool to obtain high quality biopsies of lung parenchyma in order to diagnose micronodular lesions of the lung.